Getting to the Root of the issue - Dorsal Root Ganglionitis

When I was embarking on this journey of mine, some 15 years or so ago, it seemed then that if only some proof was forthcoming, some unequivocal proof, some evidence, of a pathological nature, that could back-up the then prevalent name and associated definition attached to my diagnosis: myalgic encephalomyelitis.

If only, right? Pretty sure it's what we and our doctors for that matter want. Because with a 'root' cause or evidence of something, anything, that might be involved in our debilitation, of a biological nature (obviously ) we might stand a far better chance of getting an effective treatment, and if not that, then maybe a least greater acceptance and understanding in the wider social world.

Validity, right? Well, for some it looked like this might be the case with the handful (less than a handful) of autopsies that showed evidence of this basal root ganglionitis. I mean it's an 'itis', right? Encephalomyelitis, is one too? And the Basal Ganglia are kind of near the spine and associated with the nervous system, right?

I've seen this association, this hope, variously stated across the internet. Unfortunately, most of the instances in which it has been used have tended to try and throw it at arguments pertaining to nomenclature: "What about dorsal root ganglionitis? THAT's proof of ME!"

Most recently, the other day, I happened across this little 'gem' from ME Advocacy:

The encephalomyelitis in ME

"...In ME, autopsies have already demonstrated that dorsal root ganglionitis, which is the result of inflammatory processes targeting the sensory ganglia, is present in patients. Dorsal root ganglionitis is an alternative name for sensory ganglionitis, which may occur as a result on inflammation caused by HIV...."

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I am no doctor or neurologist (obviously) and to be honest I didn't know or understand enough about the pathology to be able to comment for the most part, other than to say that until more autopsies were performed, a couple of instances will not sway any argument.

The only chance of more autopsy tissue being made available for significant study are - in so far as I can see - that offered by the ME Association a project which is being held-up by cost burdens (there was an update to this effect in Essential's last week).

The Biobank joint ventures won't cut the mustard - for evidence of dorsal root ganglionitis I understand you need tissue obtained from autopsy - though perhaps this 'inflammation' can be observed as is inferred above by use of some sort of scan - but I doubt it.

Anyway, so I had little knowledge and therefore did not feel confident in commenting - though I did wonder as ever I do, why people who choose to make statements didn't themselves ask those who might know before broadcasting these assumptions - but there we go: c'est la vie.

Then Dr Charles Shepherd in the latest issue of ME Essentials was asked the following question and responded (below). Don't get me wrong, it is a shame (in an obvious way) that dorsal root ganglionitis is not an example or proof of 'encephalomyelitis'. But we can't change pathology no matter how much easier we hope it might make things.

Still, evidence is evidence and hopefully more autopsies will be volunteered, tissue collected, and studied with appropriate power.

Of course dorsal root ganglionitis might be only part of the puzzle, and for some people, some of the time. But I'll take something over nothing any day of the week

Reproduced with kind permission from Dr Shepherd and with thanks to the person who posed the question.

Question: I've followed the post-mortem research that you are involved with and noted that there are regular references to dorsal root ganglionitis being found in some of the tissues that have been examined.

Please could you explain what this means? And does this finding confirm that people with ME have inflammation (the -myelitis in encephalomyelitis) in the spinal cord?

Answer:

Dorsal root ganglionitis means that there is inflammation (-itis) in a part of the peripheral nervous system called a dorsal root ganglion.

A dorsal root ganglion is a bundle of nerve fibres that sits on one of the nerve roots that enter or leave the spinal cord. This is the long nerve that passes down the back inside the bony vertebrae - it sends and receives information to and from the brain.

The nerve roots that enter and leave the spinal cord have two main functions. Incoming information is largely sensory - relating to things like pain and touch - whereas out-going information largely concerns the passing on of instructions, e.g. creating muscle movements. Dorsal refers to the back of the spinal cord.

A dorsal root ganglion forms part of the sensory nerve root that enters the spinal cord - so it's involved in processing sensory information.

Inflammation in a DRG could therefore result in some of the sensory symptoms that occur in ME - pain, loss of sensation, abnormal sensations (paraesthesiae).

It's also interesting to note that the presence of dorsal root ganglionitis in Sjorgen's Syndrome has been linked to a peripheral neuropathy sometimes seen in this condition.

Although ganglionitis means inflammation, and this may well involve infection, the relationship to ME/CFS remains uncertain as this is only a preliminary finding in a small number of post-mortem cases.

A number of infections can cause ganglionitis - so it could have been caused by a previous infection not even related to ME.

As the DRG are anatomically outside the spinal cord, this finding is not the same as having inflammation in the spinal cord.

So, while the finding does support a role for inflammation in the nervous system for ME/CFS, it does not mean that spinal cord inflammation is also present.

From what I recall, autopsies on couple of folk from the London hospital outbreak in the 1950s (who died a year or two afterwards) showed inflammation of that same area?
and it's been ignored for 60 years...
Sigh

From what I recall, autopsies on couple of folk from the London hospital outbreak in the 1950s (who died a year or two afterwards) showed inflammation of that same area?
and it's been ignored for 60 years...
Sigh

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I don't know about that Silverblade. What I do know is that my own frustration has ever been that it's taken so bloody long to get folk to look where I would have surely looked in the first place god-dammit!

Let's dig up bodies! Seriously, I know autopsies are hard and expensive but let's get cracking now for heaven's sake. And what's up with not doing some studies employing whatever scans? Having said that I know we've had recent publications revealing issues with brain matter and the loike - but are these being followed-up? Or are they going to be left as 'interesting' and lead nowhere?

All very frustrating. But as I said, evidence is evidence wherever and whatever it amounts to. We just gotta do it more often, bigger and better.

DRG if found as a 'common factor' will need to be compared to 'controls' presumably and as Shepherd notes - the possibility of an external infection ruled out.

The role and function of DRG in relation to reported ME symptoms will also need to be tied together and an aetiological hypothesis formulated.

Once again, it is very early days and clearly even in the (Four?) cases studied not all those deceased patients had this inflammation. So.... But we can't really conclude much. And that's kind of the disappointing point really.

Well to be humerous too Firestormm - 10 years ago with MRI brain scans revealing "intense high" areas (my Neurologist could not explain) very ill indeed, so did consider a donation to science. But the hunt for bio-markers is well on (various researchers) and dorsal root ganglia investgation was the subject of one of Cort's articles a little while ago. HERE.

Well to be humerous too Firestormm - 10 years ago with MRI brain scans revealing "intense high" areas (my Neurologist could not explain) very ill indeed, so did consider a donation to science. But the hunt for bio-markers is well on (various researchers) and dorsal root ganglia investgation was the subject of one of Cort's articles a little while ago. HERE.

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Thank you Enid. What's become of Cort? Not seen him around for a while. Hope he's all right (relatively speaking). Yes. I'd forgotten the hypothesis from the Lights. Be good to hear more about this from them. Presumably, (I can't recall), they are not looking at autopsy tissue but exploring this my other means i.e. by way of genes?

Similar spinal lesions were also found in animals injected with patient blood after the Adelaide atypical polio epidemic. Go figure. This was published in 1955. I think I recall the lesions were found in monkeys spines, but not in other animals.

Similar spinal lesions were also found in animals injected with patient blood after the Adelaide atypical polio epidemic. Go figure. This was published in 1955. I think I recall the lesions were found in monkeys spines, but not in other animals.

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Errr.... are we talking about 'spinal lesions' here then Alex? I'm not sure we are. DRG isn't defined as a 'lesion' in anything that I have read, but if it is regarded as such then please let me know.

@ Firestormm - I see Cort pops in and out so hopefully resettled now.
From memory all sorts of investgations going on - spinal fluids, abnormal protein identifications etc.
certainly my Neurologist was prepared to release all his findings - MRIs, lumbar puncture fluid etc if I
could find an ME specialist. I'm now a Mikovits et al fan - non-HIV Autoimmune Deficiency since at
worst some latent viruses appeared, polio-like, chicken-pox like etc. But what sets off ?

Also I've no doubt about some genetic component (or weakness) - my brother overseas developed a year later than I, and a cousin has recently developed FM. Somehow I see all on the same spectrum. But still left wondering quite what was the switch from good health all round, viral in one form or another my guess, and my Neurologist thought.

From memory all sorts of investgations going on - spinal fluids, abnormal protein identifications etc. certainly my Neurologist was prepared to release all his findings - MRIs, lumbar puncture fluid etc if I could find an ME specialist. I'm now a Mikovits et al fan - non-HIV Autoimmune Deficiency since at
worst some latent viruses appeared, polio-like, chicken-pox like etc. But what sets off ?

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I am pleased to hear of any neurologist (or other specialist) engaging with patients like this and remaining open minded and willing to investigate.

I think, Enid, my own feelings towards Mikovits are rather clear by now and they certainly haven't changed after that interview the other day. Still I wish you well and hope you aren't disappointed by following what could well turn out to be another wild goose chase. We naturally become a rather thick-skinned people I believe and not out of choice.

Still. Faith, hope and money are not in endless supply, unlike opinions from 'experts' which are infinite. Bit of a minefield we have to negotiate isn't it? Anyway, all the best and I hope you get some answers.

Errr.... are we talking about 'spinal lesions' here then Alex? I'm not sure we are. DRG isn't defined as a 'lesion' in anything that I have read, but if it is regarded as such then please let me know.

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FURTHER INVESTIGATIONS ON A DISEASE
RESEMBLING POLIOMYELITIS SEEN IN
ADELAIDE.
By R. A. A. PELLEw,
Royal Adelaide Hospital,
AND
J. A. R. MILEs
Institute of Medical and Veterinary Science,
Adelaide.

"However, there were lesions
in the nerve roots and in the sciatic nerves. In the nerve
roots close to their point of exit from the spinal canal there
was pronounced infiltration with lymphocytes and mononuclear
cells, and in a percentage of the nerve fibres were
found vacuoles in the myelin sheaths and axon swellings.
In the sciatic nerves there were small localized infiltrations
with inflammatory cells associated with exudation of a few
red blood corpuscles. The only abnormality in the skeletal
muscle was the presence of sarcosporidiosis in all sections
from one animal; but examination of the heart muscle of
the monkey which had died showed severe myocarditis with
widespread infiltration mainly with lymphocytes and mononuclear
cells."

I cannot give you a link to the paper, but I can send you a copy via PR conversation, along with the paper that described the Adelaide epidemic itself. When I referred to spine I was talking about the spinal nerves, and these pass from brain to body via root ganglia.

"Definition:Lesion is a non-specific term used in medicine to refer to a pathology of tissue. It indicates an area of tissue that has been injured, destroyed, altered (for the worse) or has a problem."

Lesion is a non-specific word meaning localized injury. I use it because we really don't know the nature of the damage, only that we can see damage.

This study has to be my best match alex - from my few test findings (well more than many) and recalling muscle function tests and excrutiating pain as the current passed up the spine and one Doc convinced of myelin sheath damage. Heart racing or slowing, lungs (as muscle) affected too. If only they could pursue.

Early in my CFS years my doctor did a test that showed positive antibodies to myelin sheath..............and there was definite myelin sheath damage..........as evident by the fact that I no longer can feel touch the way I used to. Hard to describe but when something touches my skin..........it doesn't feel normal....and this is uniform all over my body. It's as if I have a barrier or film on my skin. Thank god the damage did not get any more severe to where I couldn't feel anything............I can still feel hot and cold just normal skin sensation is not the same. I have only come across one other person that this happened to.

Potentially any viral trigger I suppose could be responsible but the point is that this DRG might not even be an issue for all or many of us. It could be something unconnected.

Nobody has to my knowledge advanced a theory on 'ME' embracing DRG.l There simply is not enough evidence to make an association even if you relieve yourself of the burden of 'encephalomyelitis' which presumably you would need to do.

We are talking about only 4 autopsies performed to date by the ME Association. I'll dig out the exact results (it was a Word document and I can't bloody find the thing this morning!) as I can't recall how many instances of DRG were determined from those 4.

Chronic Fatigue Syndrome / Myalgic Encephalomyelitis is a disorder characterised by chronic exercise induced fatigue, cognitive dysfunction, sensory disturbances and often pain. The aetiology and pathogenesis are not understood.

We report the post mortem pathology of four cases of CFS diagnosed by specialists. The causes of death were all unnatural and included: suicidal overdose, renal failure due to lack of food and water, assisted suicide and probable poisoning.

Selected portions of tissue were made available by the various Coroners in the UK and with the assent of the persons in a qualifying relationship.

One case showed a vast excess of corpora amylacea in spinal cord and brain of unknown significance but Polyglucosan Body Disease was not supported by clinicopathologial review. No ganglionitis was identified.

One case showed a marked dorsal root ganglionitis and two other cases showed mild excess of lymphocytes with nodules of nageotte in the dorsal root ganglia.

This raises the hypothesis that dysfunction of the sensory and probably also the autonomic nervous system may lead to abnormal neural activity eg hyperalgesia & allodynia rather than anaesthesia and may explain some of the symptoms of CFS / ME such as pain, hypotension, hyperacusis and photophobia. However, the syndrome may be heterogeneous.

Nevertheless, the precise relationship of fatigue, which may be either peripheral or central, to abnormalities in the peripheral nervous system (PNS) needs to be studied.

The differential diagnosis of ganglionitis should be investigated in CFS / ME patients hence Varicella Zoster, Lyme disease, HIV, Sjogren’s disease, paraneoplastic sensory ganglionopathy should be excluded by appropriate history and tests.

Thorough histopathological study of cases coming to autopsy may help to confirm or refute the hypothesis, that CFS is a disease process, and whether the symptomatology may be explained by inflammation of the sensory and autonomic divisions of the PNS.
A specific CFS / ME brain and tissue bank in the UK is proposed.

One of the questions that always has to be asked about these things is whether ganglionitis is a cause of ME, a consequence of ME (complication) or associated with ME due to some underlying process that predisposes to both. The science still can't say. What cannot be disputed though is this is an important clue. An unusual result like this gives a clue to underlying pathology.

A while ago I learned about deep dorsal ganglionitis whilst watching the dvd Voices in the shadows. It got me thinking, as I had inflammation in certain areas of my skull and spine which seemed to feel lilke it spread from those areas, around my body.
I booked myself in with a chiro/mctimony person, had three sessions over six weeks. The inflammation and pain went. It hasnt happened since.
He realigned my spine, it wasnt out much, just slightly.

This got me thinking was it my misalignment from the spine causing pressure on the nerves which caused the inflammation, or was it the inflammation of the nerves causing individual parts of my spine to be moved slightly.

I had a head injury a few years ago, hit back of head on stone track from falling off pony. A lot of compression and problems undiagnosd for 18 months.
I also had the polio drops and general vaccs.
I'm 47.(originally put 57 )

I'm not writing this to ask for an answer, just thought it may be of interest and adding to the discussion with the ganglionitis connection.